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An Investigational Drug, PF-02341066 Is Being Studied Versus Standard Of Care In Patients With Advanced Non-Small Cell Lung Cancer With A Specific Gene Profile Involving The Anaplastic Lymphoma Kinase (ALK) Gene

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT00932893
First received: June 30, 2009
Last updated: April 11, 2016
Last verified: April 2016
Results First Received: March 13, 2013  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Carcinoma, Non-Small-Cell Lung
Interventions: Drug: PF-02341066
Drug: Pemetrexed
Drug: Docetaxel

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Crizotinib Crizotinib (PF-02341066) 250 mg (administered as two 100-mg tablets and one 50-mg tablet) orally twice daily continuously in 21-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred.
Chemotherapy Pemetrexed 500 mg per square meter (mg/m^2) intravenous infusion over 10 minutes or docetaxel 75 mg/m^2 intravenous infusion over 1 hour on Day 1 of 21-day cycle, as per investigator discretion. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred.

Participant Flow:   Overall Study
    Crizotinib   Chemotherapy
STARTED   173   174 
Treated   172   171 
COMPLETED   0   0 
NOT COMPLETED   173   174 
Death                46                16 
Lost to Follow-up                1                0 
Withdrawal by Subject                3                2 
Unspecified                5                107 
Ongoing at Data Cut-off                118                49 



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full analysis set (FAS) included all participants who were randomized to study treatment.

Reporting Groups
  Description
Crizotinib Crizotinib (PF-02341066) 250 mg (administered as two 100-mg tablets and one 50-mg tablet) orally twice daily continuously in 21-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred.
Chemotherapy Pemetrexed 500 mg/m^2 intravenous infusion over 10 minutes or docetaxel 75 mg/m^2 intravenous infusion over 1 hour on Day 1 of 21-day cycle, as per investigator discretion. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred.
Total Total of all reporting groups

Baseline Measures
   Crizotinib   Chemotherapy   Total 
Overall Participants Analyzed 
[Units: Participants]
 173   174   347 
Age 
[Units: Years]
Mean (Standard Deviation)
 50.31  (13.1)   49.81  (13.0)   50.06  (13.0) 
Gender 
[Units: Participants]
     
Female   98   96   194 
Male   75   78   153 


  Outcome Measures
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1.  Primary:   Progression-Free Survival (PFS)   [ Time Frame: Randomization until progressive disease (PD) or initiation of antitumor therapy in the absence of PD or death, assessed every 6 weeks (up to 112 weeks) ]

2.  Secondary:   Overall Survival (OS)   [ Time Frame: Randomization until death (up to 112 weeks) ]

3.  Secondary:   Overall Survival Probability at Month 6 and Month 12   [ Time Frame: Month 6, 12 ]

4.  Secondary:   Percentage of Participants With Objective Response (OR)   [ Time Frame: Randomization until PD or initiation of antitumor therapy in the absence of PD or death, assessed every 6 weeks (up to 112 weeks) ]

5.  Secondary:   Percentage of Participants With Disease Control at Week 6   [ Time Frame: Week 6 ]

6.  Secondary:   Percentage of Participants With Disease Control at Week 12   [ Time Frame: Week 12 ]

7.  Secondary:   Duration of Response (DR)   [ Time Frame: Randomization until PD or initiation of antitumor therapy in the absence of PD or death, assessed every 6 weeks (up to 112 weeks) ]

8.  Secondary:   Time to Tumor Response (TTR)   [ Time Frame: Randomization until PD or initiation of antitumor therapy in the absence of PD or death, assessed every 6 weeks (up to 112 weeks) ]

9.  Secondary:   Pre-Dose Plasma Concentration (Ctrough) of Crizotinib   [ Time Frame: Pre-dose on Day 1 of Cycle 1, 2, 3, 5 ]

10.  Secondary:   Pre-Dose Plasma Concentration at Steady State (Ctrough, ss) of Crizotinib   [ Time Frame: Pre-dose on Day 15 of Cycle 1 ]

11.  Secondary:   Number of Participants With Categorical Maximum QTcF for Crizotinib   [ Time Frame: Pre-dose on Day 1 of Cycle 1, 2 to 6 hours post-dose on Day 1 of Cycle 1, 2 ]

12.  Secondary:   Time to Deterioration (TTD) in Participant Reported Pain, Dyspnea, and Cough   [ Time Frame: Baseline up to end of treatment (up to 112 weeks) ]

13.  Secondary:   European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30)   [ Time Frame: Baseline, Day (D) 1 of each cycle (C) until disease progression, end of treatment (EOT, up to 112 weeks) ]

14.  Secondary:   European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Supplement Module for Lung Cancer (EORTC QLQ-LC13)   [ Time Frame: Baseline, Day 1 of each cycle until disease progression, end of treatment (up to 112 weeks) ]

15.  Secondary:   European Quality of Life - 5 Dimensional (EQ-5D) Visual Analog Scale (VAS)   [ Time Frame: Baseline, Day 1 of each cycle until disease progression, end of treatment (up to 112 weeks) ]

16.  Secondary:   Percentage of Participants With Echinoderm Microtubule Associated Protein-Like 4-Anaplastic Lymphoma Kinase (EML4-ALK) Fusion Variants   [ Time Frame: Pre-dose on Day 1 of Cycle 1, 2 to 6 hours post-dose on Day 1 of Cycle 2, end of treatment (up to 112 weeks) ]
Results not yet reported.   Anticipated Reporting Date:   01/2017   Safety Issue:   No

17.  Secondary:   Plasma Concentration of Soluble c-Met Ectodomain and Hepatocyte Growth Factor Scatter Proteins   [ Time Frame: Pre-dose on Day 1 of Cycle 1, 2 to 6 hours post-dose on Day 1 of Cycle 2, end of treatment (up to 112 weeks) ]
Results not yet reported.   Anticipated Reporting Date:   01/2017   Safety Issue:   No


  Serious Adverse Events


  Other Adverse Events
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Time Frame No text entered.
Additional Description The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.

Frequency Threshold
Threshold above which other adverse events are reported   5  

Reporting Groups
  Description
Crizotinib Crizotinib (PF-02341066) 250 mg (administered as two 100-mg tablets and one 50-mg tablet) orally twice daily continuously in 21-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred.
Chemotherapy Pemetrexed 500 mg/m^2 intravenous infusion over 10 minutes or docetaxel 75 mg/m^2 intravenous infusion over 1 hour on Day 1 of 21-day cycle, as per investigator discretion. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred.

Other Adverse Events
    Crizotinib   Chemotherapy
Total, other (not including serious) adverse events     
# participants affected / at risk   169/172 (98.26%)   154/171 (90.06%) 
Blood and lymphatic system disorders     
Anaemia * 1     
# participants affected / at risk   25/172 (14.53%)   26/171 (15.20%) 
Leukopenia * 1     
# participants affected / at risk   15/172 (8.72%)   9/171 (5.26%) 
Neutropenia * 1     
# participants affected / at risk   35/172 (20.35%)   17/171 (9.94%) 
Eye disorders     
Photopsia * 1     
# participants affected / at risk   17/172 (9.88%)   1/171 (0.58%) 
Vision blurred * 1     
# participants affected / at risk   14/172 (8.14%)   5/171 (2.92%) 
Visual impairment * 1     
# participants affected / at risk   81/172 (47.09%)   9/171 (5.26%) 
Gastrointestinal disorders     
Abdominal pain * 1     
# participants affected / at risk   15/172 (8.72%)   8/171 (4.68%) 
Abdominal pain upper * 1     
# participants affected / at risk   9/172 (5.23%)   12/171 (7.02%) 
Constipation * 1     
# participants affected / at risk   73/172 (42.44%)   39/171 (22.81%) 
Diarrhoea * 1     
# participants affected / at risk   103/172 (59.88%)   33/171 (19.30%) 
Dyspepsia * 1     
# participants affected / at risk   14/172 (8.14%)   6/171 (3.51%) 
Nausea * 1     
# participants affected / at risk   94/172 (54.65%)   62/171 (36.26%) 
Stomatitis * 1     
# participants affected / at risk   7/172 (4.07%)   12/171 (7.02%) 
Vomiting * 1     
# participants affected / at risk   79/172 (45.93%)   30/171 (17.54%) 
General disorders     
Asthenia * 1     
# participants affected / at risk   25/172 (14.53%)   32/171 (18.71%) 
Chest pain * 1     
# participants affected / at risk   9/172 (5.23%)   12/171 (7.02%) 
Fatigue * 1     
# participants affected / at risk   46/172 (26.74%)   56/171 (32.75%) 
Oedema * 1     
# participants affected / at risk   11/172 (6.40%)   5/171 (2.92%) 
Oedema peripheral * 1     
# participants affected / at risk   44/172 (25.58%)   14/171 (8.19%) 
Pyrexia * 1     
# participants affected / at risk   30/172 (17.44%)   32/171 (18.71%) 
Infections and infestations     
Nasopharyngitis * 1     
# participants affected / at risk   24/172 (13.95%)   6/171 (3.51%) 
Upper respiratory tract infection * 1     
# participants affected / at risk   16/172 (9.30%)   15/171 (8.77%) 
Investigations     
Alanine aminotransferase increased * 1     
# participants affected / at risk   62/172 (36.05%)   20/171 (11.70%) 
Aspartate aminotransferase increased * 1     
# participants affected / at risk   45/172 (26.16%)   16/171 (9.36%) 
Blood alkaline phosphatase increased * 1     
# participants affected / at risk   13/172 (7.56%)   6/171 (3.51%) 
Blood creatinine increased * 1     
# participants affected / at risk   12/172 (6.98%)   3/171 (1.75%) 
Neutrophil count decreased * 1     
# participants affected / at risk   12/172 (6.98%)   9/171 (5.26%) 
Weight decreased * 1     
# participants affected / at risk   17/172 (9.88%)   6/171 (3.51%) 
White blood cell count decreased * 1     
# participants affected / at risk   12/172 (6.98%)   13/171 (7.60%) 
Metabolism and nutrition disorders     
Decreased appetite * 1     
# participants affected / at risk   47/172 (27.33%)   44/171 (25.73%) 
Hyperglycaemia * 1     
# participants affected / at risk   5/172 (2.91%)   9/171 (5.26%) 
Hypoalbuminaemia * 1     
# participants affected / at risk   11/172 (6.40%)   1/171 (0.58%) 
Hypokalaemia * 1     
# participants affected / at risk   9/172 (5.23%)   4/171 (2.34%) 
Musculoskeletal and connective tissue disorders     
Arthralgia * 1     
# participants affected / at risk   11/172 (6.40%)   20/171 (11.70%) 
Back pain * 1     
# participants affected / at risk   18/172 (10.47%)   12/171 (7.02%) 
Musculoskeletal pain * 1     
# participants affected / at risk   12/172 (6.98%)   5/171 (2.92%) 
Myalgia * 1     
# participants affected / at risk   3/172 (1.74%)   18/171 (10.53%) 
Pain in extremity * 1     
# participants affected / at risk   9/172 (5.23%)   10/171 (5.85%) 
Nervous system disorders     
Dizziness * 1     
# participants affected / at risk   28/172 (16.28%)   12/171 (7.02%) 
Dysgeusia * 1     
# participants affected / at risk   44/172 (25.58%)   16/171 (9.36%) 
Headache * 1     
# participants affected / at risk   32/172 (18.60%)   25/171 (14.62%) 
Neuropathy peripheral * 1     
# participants affected / at risk   4/172 (2.33%)   9/171 (5.26%) 
Paraesthesia * 1     
# participants affected / at risk   10/172 (5.81%)   7/171 (4.09%) 
Psychiatric disorders     
Insomnia * 1     
# participants affected / at risk   18/172 (10.47%)   14/171 (8.19%) 
Respiratory, thoracic and mediastinal disorders     
Cough * 1     
# participants affected / at risk   28/172 (16.28%)   33/171 (19.30%) 
Dyspnoea * 1     
# participants affected / at risk   18/172 (10.47%)   28/171 (16.37%) 
Epistaxis * 1     
# participants affected / at risk   2/172 (1.16%)   10/171 (5.85%) 
Haemoptysis * 1     
# participants affected / at risk   6/172 (3.49%)   11/171 (6.43%) 
Oropharyngeal pain * 1     
# participants affected / at risk   13/172 (7.56%)   7/171 (4.09%) 
Rhinorrhoea * 1     
# participants affected / at risk   4/172 (2.33%)   9/171 (5.26%) 
Skin and subcutaneous tissue disorders     
Alopecia * 1     
# participants affected / at risk   14/172 (8.14%)   35/171 (20.47%) 
Dry skin * 1     
# participants affected / at risk   9/172 (5.23%)   2/171 (1.17%) 
Pruritus * 1     
# participants affected / at risk   9/172 (5.23%)   7/171 (4.09%) 
Rash * 1     
# participants affected / at risk   15/172 (8.72%)   29/171 (16.96%) 
* Events were collected by non-systematic assessment
1 Term from vocabulary, MedDRA 15.0



  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
These results are from a preliminary clinical study report including final results for PFS and interim results for OS.


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